Activation of the C Attack Mechanism

Since the C attack mechanism seems to assemble spontaneously on cleavage of native C5, any enzyme which can produce C5b may activate the sequence. However, the most thoroughly studied activators are the complex enzymes of the complement system for which C5 can be considered the natural substrate.  

The requirement for two associated C3b molecules in the alternative pathway C5 convertase seems to restrict formation of this enzyme to the surface of particulate C activators where association of C3b may occur more readily. Even in the presence of stabilizing factors such as P, fluid-phase C5 convertase activity is very low. However, cobra venom factor, a C3b analogue (Alper and Balavitch, 1976), forms an efficient fluid-phase C5 convertase in association with factor B, perhaps because of the association or aggregation of the CoVF-Bb enzyme (Medicus, 1977). 

Other enzymes may also possess C5 convertase activity. For example, it has been reported that a fragment of properdin generated by the action of an enzyme, properdin convertase, can directly cleave C5 in the absence of other serum cofactors (Spitzer et aL, 1976). Plasmin and trypsin have been shown to generate C567 when incubated with the purified components (Arroyave and Miiller-Eberhard, 1973), and leukocyte lysosomal enzymes have been shown to generate chemotactic activity from C5, presumably C5a (Goldstein and Weissmann, 1974) it is likely that they also generate C5b (Arroyave and Miiller-Eberhard, 1973) and initiate the assembly of the C attack mechanism. 

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